Synthesis of Hybrid Fluoroquinolone-Boron Complexes and Their Evaluation in Cervical Cancer Cell Lines

Abstract

Quinolones are a family of antimicrobial agents that have been used in antibacterial and anticancer chemotherapy. Fluoroquinolone targets DNA gyrase and topoisomerase IV enzymes affecting several cellular processes, like cell death and proliferation; the best way to act is in the form of carboxylic acid or, recently, as quinolone-metal complex. In this work, the use of boron is shown as an alternative of metal to form a complex by incorporating to fluoroquinolone as an electron withdrawing substituent to activate the C-7 position chemoselectively for the production of new fluoroquinolone hybrids and test their effects on cell proliferation. Fluoroquinolone-boron complexes were synthesized according to the Gould-Jacobs cyclization method, and five hybrid fluoroquinolone-boron compounds were obtained by S N Ar reaction, yielding 31 to 46%, at 80°C, and in 10 to 25 hours of reaction. e effect of the five fluoroquinolone-boron hybrids was evaluated in cervical cancer cell lines by cell proliferation assay. 7-hydantoin-fluoroquinolone-boron and 7-dihydropyridine-fluoroquinolone-boron complexes showed the strongest effect according to dose-response assay, respectively. e fluoroquinolone-boron hybrid complex showed proliferation inhibition in SiHa and CasKi cells, opening the possibility to use them as potential agents for the treatment of cancer.

Combined Effects of Zoledronic Acid and Sodium Pentaborate Pentahydrate on Proliferation, Migration and Apoptosis of Human Neuroblastoma Cell Line

“…Up to now, developmental benefits of the B have been shown in various studies [19,20]. B compounds have been used in prostate, lung, cervical, and breast cancer and caused positive effects against cancer [11,13,[21][22][23]. The supporting effect of B was demonstrated in patients who received chemotherapy [11].…”

Towards anticancer fluoroquinolones: A review article

“…Boron complexes of some C7 modified fluoroquinolones achieved the antiproliferative activity on the human cervical carcinoma SiHa and CasKi cell lines. Hydantoin and dihydropyridine functionalized derivatives, compounds 59 and 60 , experienced the highest activity toward SiHa and CasKi cell lines, respectively at 0.75 mM after 72 hr of incubation . 1,10‐Phenanthroline and 2,2'‐bipyridyl copper(II) complexes with sparafloxacin were also potent antitumor agents.…”

Synthesis and Anticancer Activity of 1‐(Ethyl/Methyl)‐7‐(p‐Methoxybenzyl Amino) and 7‐Amino‐6‐Fluoroquinolone‐Boron Difluoride Complexes

“…Boron has been shown to strengthen the immune system, improve brain functions, modify hormone levels, and prevent osteoporosis, rheumatism, and vaginal infections in humans. Cancer treatments featuring boron, known as boron neutron capture therapy (BNCT), have been successful in treating cancerous cells with minimum damage to healthy cells tissues, [26–29] few examples of fluoroquinolone derivatives containing boron‐based substituents have been reported in the literature [30–33] …”

“…Cancer treatments featuring boron, known as boron neutron capture therapy (BNCT), have been successful in treating cancerous cells with minimum damage to healthy cells tissues, [26][27][28][29] few examples of fluoroquinolone derivatives containing boron-based substituents have been reported in the literature. [30][31][32][33] On the one hand, only a few fluoroquinolone-boron compounds exhibited antibacterial activity, [33] or antiproliferative activity in cancerous cell strains. [30] On the other hand, molecular docking calculations of derivatives of norfloxacinboron complexes with vascular endothelial growth factor receptor (VEGFRTK) showed that boron nuclei allowed a favorable interaction with the receptor; [34] this interaction was enhanced when the boron atom is bonded to fluorine atoms.…”